Pre-existing osteoporosis and serum vitamin D levels in patients with distal radius fractures: are we missing something?

INTRODUCTION: Given the significant therapeutic gap for osteoporosis, this study aims to investigate the most common osteoporosis-related fracture. The analysis will also consider patients' serum vitamin D levels and the indications for basic osteoporosis diagnostic tests and osteoporosis therapy prior to fracture. MATERIALS AND METHODS: This prospective clinical trial included patients with distal radius fractures who underwent surgery at our hospital between 1 April 2021 and 7 April 2022. Blood samples were taken from all participants and existing risk factors for osteoporosis were recorded. In addition, the indication for a guideline-based osteoporosis diagnosis was assessed and the risk of another future fracture with FRAX® was calculated. This information was used to decide whether there was an indication for specific osteoporosis therapy. RESULTS: A diagnosis gap of 53% and a treatment gap of 84% were identified among the 102 patients investigated. The patients' ages ranged from 46 to 91 years, with an average vitamin D level of 57 nmol/l, which was below the recommended level of 75 nmol/l. It was noted on a monthly basis that the vitamin D level (without substitution) never exceeded the recommended value of 75 nmol/l in any month. Three-quarters of patients had indications for a baseline osteoporosis diagnosis, yet less than 50% received one. According to FRAX® data, 57% of patients had indications for specific osteoporosis treatment before experiencing the fracture. CONCLUSION: Even without a previous distal radius fracture, many patients are in need of osteoporosis diagnosis or treatment. Our research suggests that patients with distal radius fractures should have their vitamin D levels checked via a blood test and be evaluated for osteoporosis. As endogenous vitamin D levels are often inadequate, year-round vitamin D supplementation should be considered for the prevention of osteomalacia and as a basis for the treatment of osteoporosis. GERMAN CLINICAL TRIAL REGISTER ID: DRKS00028085.

The standardized creation of a lumbar spine vertebral compression fracture in a sheep osteoporosis model induced by ovariectomy, corticosteroid therapy and calcium/phosphorus/vitamin D-deficient diet.

INTRODUCTION: Vertebral compression fractures (VCFs) are one of the most common injuries in the aging population presenting with an annual incidence of 1.4 million new cases in Europe. Current treatment strategies focus on cement-associated solutions (kyphoplasty/vertebroplasty techniques). Specific cement-associated problems as leakage, embolism and the adjacent fracture disease are reported adding to open questions like general fracture healing properties of the osteoporotic spine. In order to analyze those queries animal models are of great interest; however, both technical difficulties in the induction of experimental osteoporosis in animal as well as the lack of a standardized fracture model impede current and future in vivo studies. This study introduces a standardized animal model of an osteoporotic VCF type A3.1 that may enable further in-depth analysis of the afore mentioned topics. MATERIAL AND METHODS: Twenty-four 5-year-old female Merino sheep (mean body weight: 67 kg; range 57-79) were ovariectomized (OP1) and underwent 5.5 months of weekly corticosteroid injections (dexamethasone and dexamethasone-sodium-phosphate), adding to a calcium/phosphorus/vitamin D-deficient diet. Osteoporosis induction was documented by pQCT and micro-CT BMD (bone mineral density) as well as 3D histomorphometric analysis postoperatively of the sheep distal radius and spine. Non osteoporotic sheep served as controls. Induction of a VCF of the second lumbar vertebra was performed via a mini-lumbotomy surgical approach with a standardized manual compression mode (OP2). RESULTS: PQCT analysis revealed osteoporosis of the distal radius with significantly reduced BMD values (0.19 g/cm(3), range 0.13-0.22 vs. 0.27 g/cm(3), range 0.23-0.32). Micro-CT documented significant lowering of BMD values for the second lumbar vertebrae (0.11 g/cm(3), range 0.10-0.12) in comparison to the control group (0.14 g/cm(3), range 0.12-0.17). An incomplete burst fracture type A3.1 was achieved in all cases and resulted in a significant decrease in body angle and vertebral height (KA 4.9°, range: 2-12; SI 4.5%, range: 2-12). With OP1, one minor complication (lesion of small bowel) occurred, while no complications occurred with OP2. CONCLUSIONS: A suitable spinal fracture model for creation of VCFs in osteoporotic sheep was developed. The technique may promote the development of improved surgical solutions for VCF treatment in the experimental and clinical setting.

Acute effects of N-acetylcysteine on skeletal muscle microcirculation following closed soft tissue trauma in rats.

Trauma-induced microcirculatory dysfunction, formation of free radicals and decreased endothelial release of nitric oxide (NO) contribute to evolving tissue damage following skeletal muscle injury. Administration of N-acetylcysteine (NAC) known to scavenge free radicals and generate NO is considered a valuable therapeutic approach. Thus, the objective of this study was to quantitatively analyze the acute effects of NAC on skeletal muscle microcirculation and leukocyte-endothelial cell interaction following severe standardized closed soft tissue injury (CSTI). Severe CSTI was induced in the hindlimbs of 14 male anesthetized Sprague-Dawley rats using the controlled impact injury technique. Rats were randomly assigned (n = 7) to high-dose intravenous infusion of NAC (400 mg/kg body weight) or isovolemic normal saline (NS). Non-injured, sham-operated animals (n = 7) were subjected to the same surgical procedures but did not receive any additional fluid. Creatin kinase (CK) activity was assessed at baseline, 1 h before and 2 h following posttraumatic NAC or NS infusion. Microcirculation of the extensor digitorum longus (EDL) muscle was analyzed using intravital microscopy and Laser-Doppler flowmetry (LDF). Edema index (EI) was calculated by measuring the EDL wet-to-dry weight ratio (EI=injured/contralateral limb). EDL-muscles were analyzed for desmin immunoreactivity and granulocyte infiltration. Microvascular deteriorations observed following NS-infusion were effectively reversed by NAC: Functional capillary density was restored to levels found in sham-operated animals and leukocyte adherence was significantly (p < 0.05) reduced compared to the NS group. NAC significantly (p < 0.05) increased erythrocyte flux determined by Laser-Doppler flowmetry. Posttraumatic serum CK levels and EI were significantly (p < 0.05) decreased by NAC. During the posttraumatic acute phase, single infusion of NAC markedly reduced posttraumatic microvascular dysfunction, attenuated both leukocyte adherence and tissue infiltration. NAC also decreased CSTI-induced edema formation and myonecrosis as reflected by attenuated serum CK levels and attenuated loss of desmin immunoreactivity. NAC may serve as an effective therapeutic strategy by supporting microvascular blood supply and tissue viability in the early posttraumatic period. Additional studies aimed at long-term analysis and investigation of injury severity--or dosage dependency are needed.